ライフサイエンスコーパス: EPCR

1 EPCR and EPCR-bound ligands were endocytosed rapidly via

2 EPCR and its ligand APC promote cell survival that contr

3 EPCR deficiency attenuated the elaboration of interleuki

4 EPCR deficiency in FVIII-/- mice significantly reduced t

5 EPCR expression was markedly decreased in the colon muco

6 EPCR is a major histocompatibility complex-like molecule

7 EPCR is detected in the giant trophoblast cells at the f

8 EPCR plays a crucial role in the protein C anticoagulant

9 EPCR structure contains a hydrophobic groove filled with

10 EPCR(-/-) mice were more susceptible to dextran sulfate

11 EPCR(R84A/R84A) mice are viable and reproduce normally.

12 EPCR(R84A/R84A) mice challenged with lipopolysaccharide

13 EPCR-dependent protein C activation and APC antiapoptoti

14 EPCR-mediated FVIIa endocytosis/recycling also resulted

15 EPCR/APC is a novel target of relevance in the clinical

16 abundance of parasite PfEMP1 DC8 and group A EPCR-binding domains.

17 Ad.EPCR treatment elicited recruitment of macrophages and N

18 Ad.EPCR treatment resulted in a marked increase in tumor ce

19 Intrapleural injection of Ad.EPCR into mice with an established MPM originating from

20 The acquisition of antibodies against EPCR-binding CIDRalpha1 domains of PfEMP1 after a severe

21 dependent of PC interaction, we generated an EPCR point mutation knock-in mouse (EPCR(R84A/R84A)) whi

22 may include the inhibition of NETosis in an EPCR-, PAR3-, and Mac-1-dependent manner, providing addi

23 new paradigm for understanding how PAR-1 and EPCR participate in protective signaling events in endot

24 e PfEMP1s, predicted to bind both ICAM-1 and EPCR, is associated with increased risk of developing ce

25 critical for its anticoagulant activity and EPCR-dependent barrier protection, had no effect on its

26 cause mFVIIa-FMR models the TF-dependent and EPCR binding properties of rhFVIIa, our data unmask a no

27 nding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocytosis may facilitate the transcytosi

28 EPCR and EPCR-bound ligands were endocytosed rapidly via a dynami

29 as induced in FVIII-/-, EPCR-/-FVIII-/-, and EPCR++FVIII-/- mice by needle puncture injury.

30 Our study reveals new roles for PAR1 and EPCR in controlling NO production to balance maintenance

31 Tie2 activation by FXa required PAR3 and EPCR.

32 oth protein C activation (thrombomodulin and EPCR) and APC cellular signaling (EPCR and PAR-1) pathwa

33 crease in PC activation not seen when TM and EPCR are anchored to distinct cell adhesion molecules.

34 ration of blocking antibodies against TM and EPCR significantly reduced CCM hemorrhage in Pdcd10 (ECK

35 sults in increased levels of vascular TM and EPCR, as well as in enhanced generation of activated pro

36 e pattern with VWF (paired t test for TM and EPCR, each P < .001; for VWF, P = .01).

37 orylation of Dab1 and GSK3beta, whereas anti-EPCR or anti-PAR1 blocking antibodies did not.

38 a required the enzymatic active site of APC, EPCR, and PAR-1, highlighting a key role for APC's cytop

39 Inhibition of NO production by aPC-EPCR-PAR1 signaling reduces progenitor cell egress from

40 silencing of EPCR expression or blocking APC/EPCR interaction reduced infiltration in the target orga

41 Signaling pathway triggered by APC/EPCR and its relevance in apoptosis was studied in vitro

42 Based on our findings, we believe EPCR represents the first known marker that 'explicitly'

43 n studies demonstrate an interaction between EPCR and S1P1 upon APC treatment.

44 se results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not requ

45 an prothrombin Gla domain, which cannot bind EPCR or support protein S cofactor activity, has 22/45 r

46 hrocyte membrane protein 1) family that bind EPCR, including DC8 var genes that have previously been

47 th cerebral malaria were more likely to bind EPCR and ICAM-1 than IE from children with uncomplicated

48 esidue variant, PC(PT8), also failed to bind EPCR.

49 iduals in malaria-endemic regions that block EPCR binding of diverse CIDRalpha1 variants.

50 However, the V(gamma)4V(delta)5 TCR bound EPCR independently of lipids, in an antibody-like way.

51 ing by activated protein C through PAR1, but EPCR may have additional roles by interacting with the 4

52 e impairment of the thrombomodulin-protein C-EPCR anticoagulation pathway.

53 st to other stem cell markers, such as CD38, EPCR expression is maintained when cells are introduced

54 CHO-EPCR cells and human umbilical vein endothelial cells (H

55 We combine crystal structures of CIDRalpha1:EPCR complexes with analysis of 885 CIDRalpha1 sequences

56 Conversely, EPCR expression in the embryo, without expression in the

57 In the last decade, EPCR has received wide attention after it was discovered

58 critical target of aPC therapy, and document EPCR-independent antiinflammatory effects of aPC on inna

59 . (2015) explore how diverse PfEMP1s embrace EPCR, promoting parasite survival and killing African ch

60 d hemophilia A (FVIII-/-) mice lacking EPCR (EPCR-/-FVIII-/-) or overexpressing EPCR (EPCR++ FVIII-/-

61 CR (EPCR-/-FVIII-/-) or overexpressing EPCR (EPCR++ FVIII-/-).

62 We examined EPCR levels using a microarray dataset of 107 patients.

63 oth muscle cells that constitutively express EPCR and TF, thrombin and FVIIa/FX but not FVIIa alone i

64 on in nonaggressive MPM cells that expressed EPCR and PAR1 with minimal levels of tissue factor did n

65 hat mice implanted with MPM cells expressing EPCR had elevated levels of IFNgamma and TNFalpha compar

66 s from E13.5, suggesting that extraembryonic EPCR expression may be essential for embryonic viability

67 PM cells that lack or express tissue factor, EPCR or PAR1, and an orthotopic nude mouse model of MPM.

68 udies also discovered additional ligands for EPCR, which include factor VIIa, Plasmodium falciparum e

69 s provide novel insights into mechanisms for EPCR multifunctionality.

70 confirming Leu-8 as the critical residue for EPCR recognition.

71 These data reveal an essential role for EPCR and PAR1 on hematopoietic cells, identify EPCR-expr

72 BM transplant experiments suggest a role for EPCR on hematopoietic stem cells and BM stromal cells in

73 hese findings suggest a detrimental role for EPCR-binding CIDRalpha1 domains in brain swelling.

74 observations open unsuspected new roles for EPCR in hemostasis, malaria pathogenesis, innate immunit

75 hemostatic levels of FVIIa displace PC from EPCR, and blockade of EPCR reduces the level of FVIIa ne

76 Ia), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescen

77 Joint bleeding was induced in FVIII-/-, EPCR-/-FVIII-/-, and EPCR++FVIII-/- mice by needle punct

78 ld-type mice into animals with hematopoietic EPCR deficiency restored the therapeutic efficacy of aPC

79 les showed a robust association between high EPCR levels and poor prognosis, particularly in stage I

80 tumor growth through PAR1, and they show how EPCR can attenuate the growth of tissue factor-expressin

81 he biochemical level, it remains unclear how EPCR interaction with its ligands at the cell surface im

82 Understanding how EPCR-APC induces cytoprotective effects through activati

83 (DH) site mapping across 38 kb of the human EPCR gene (hEPCR) locus identified 3 potential regulator

84 CR and PAR1 on hematopoietic cells, identify EPCR-expressing dendritic immune cells as a critical tar

85 together, our studies suggest that impaired EPCR/PC-binding interactions not only result in procoagu

86 The development of hemophilic arthropathy in EPCR-overexpressing FVIII-/- mice did not significantly

87 importance of EPCR has been demonstrated in EPCR knockout mice which show early embryonic lethality

88 aria isolates had substantial differences in EPCR binding affinity and blockade activity for its liga

89 in intron 2, was primarily hypersensitive in EPCR-negative cells, and capable of initiating antisense

90 PCh in EPCR could be exchanged for lysophosphatidylcholine (lys

91 lished whether lipid exchange takes place in EPCR as a regulatory mechanism of its activity.

92 evelopment of milder hemophilic synovitis in EPCR-/-FVIII-/- mice.

93 Interestingly, EPCR(R84A/R84A) mice develop splenomegaly as a result of

94 motes tumor cell apoptosis, and intrapleural EPCR gene therapy suppresses MPM progression.

95 xpressing tissue factor and PAR1 but lacking EPCR and PAR2 (F2RL1) generated large tumors in the pleu

96 ished MPM originating from MPM cells lacking EPCR reduced the progression of tumor growth.

97 red to mice implanted with MPM cells lacking EPCR.

98 nerated hemophilia A (FVIII-/-) mice lacking EPCR (EPCR-/-FVIII-/-) or overexpressing EPCR (EPCR++ FV

99 to in vivo challenge with LPS, mice lacking EPCR or PAR2 failed to fully initiate an interferon-regu

100 ated mice in which one allele of full-length EPCR was replaced by sEPCR (Procrs/+).

101 , increases retention of bone marrow NO(low) EPCR(+) LT-HSCs and protects mice from chemotherapy-indu

102 e maintenance and recruitment of bone marrow EPCR(+) LT-HSCs, with potential clinical relevance for s

103 It is unknown whether membrane EPCR (mEPCR) heterozygosity and/or physiologically eleva

104 logous to rhFVIIa, but binds poorly to mouse EPCR (mEPCR).

105 rated an EPCR point mutation knock-in mouse (EPCR(R84A/R84A)) which lacks the ability to bind PC/APC.

106 these domains mimic features of the natural EPCR ligand and can block this ligand interaction.

107 , PC(PT8/10) (L8V/H10K) displayed negligible EPCR affinity, despite normal binding to anionic phospho

108 activity index in the wild-type mice but not EPCR(-/-) mice.

109 D11b, PAR1, or sphingosine kinase-1, but not EPCR, abolished the ability of APC to suppress the macro

110 Bone marrow cells isolated on the basis of EPCR expression alone are highly enriched for hematopoie

111 nd subsequently fractionated on the basis of EPCR expression indicates that stem cell activity is alw

112 FVIIa displace PC from EPCR, and blockade of EPCR reduces the level of FVIIa needed for hemostasis in

113 vivo studies in mice showed that blockade of EPCR with EPCR-blocking antibodies impaired the early ph

114 Thus, the colocalization of EPCR and PAR-1 in lipid rafts is a key requirement for t

115 multimolecular stress signature composed of EPCR and costimulatory ligand(s).

116 IIa, our data unmask a novel contribution of EPCR on the action of rhFVIIa administration in hemophil

117 ild-type CD11chi dendritic cells depleted of EPCR+ cells did not.

118 Malaria-associated depletion of EPCR, with subsequent impairment of the protein C system

119 h endothelial cells leads to dissociation of EPCR from caveolin-1 and recruitment of PAR-1 to a prote

120 hropathy, administration of a single dose of EPCR-blocking monoclonal antibodies markedly reduced hem

121 negative Rab5A inhibited the endocytosis of EPCR-FVIIa.

122 Here, we show that expression of EPCR and PAR1 on hematopoietic cells is required in mice

123 found significantly increased expression of EPCR and TM in the valvular sinus endothelium as opposed

124 More importantly, ectopic expression of EPCR in aggressive MPM cells attenuated their growth pot

125 Expression of EPCR in mature murine immune cells was limited to a subs

126 Heterologous expression of EPCR promoted PAR1 and PAR2 cleavage by FXa in the terna

127 A small fraction of EPCR is also localized intracellularly in the recycling

128 is not sensitive to the cofactor function of EPCR.

129 malaria, and indicate that low impairment of EPCR function may contribute to parasite virulence.

130 The physiological importance of EPCR has been demonstrated in EPCR knockout mice which s

131 conventional dendritic cells independent of EPCR and suppressed IFN-gamma production by natural kill

132 rough the activation of PAR-2 independent of EPCR mobilization.

133 dels of TF signaling, antibody inhibition of EPCR selectively blocked PAR activation by the ternary T

134 that complementary receptor interactions of EPCR binding PfEMP1with ICAM-1 amplifies development of

135 ding to EPCR promoted the internalization of EPCR.

136 ed, cells with genetically reduced levels of EPCR no longer showed a signaling response to the ternar

137 s microvessels, we demonstrated that loss of EPCR and TM at sites of IE cytoadherence is detectible i

138 The loss of EPCR appeared to associate with increased disease index

139 CM showed cerebral fibrin clots and loss of EPCR, colocalized with sequestered IEs.

140 croscopy studies revealed that a majority of EPCR is localized on the cell surface in membrane microd

141 lipid exchange as a regulatory mechanism of EPCR activity driven by the endothelially expressed secr

142 Because of the pleiotropic nature of EPCR and TM, these data implicate disruption of the endo

143 Although engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC acti

144 Moreover, overexpression of EPCR induced an increased metastatic activity to target

145 ted and endothelial cells in the presence of EPCR.

146 hibited the barrier-protective properties of EPCR in human brain endothelial cells in vitro.

147 edly expand our understanding of the role of EPCR in normal physiology and disease, as well as provid

148 provided conflicting data about the role of EPCR in SM.

149 In order to study the role of EPCR independent of PC interaction, we generated an EPCR

150 These results underpin the significance of EPCR binding in pediatric malaria patients that require

151 In vivo, silencing of EPCR expression or blocking APC/EPCR interaction reduced

152 GTPases in the intracellular trafficking of EPCR and FVIIa.

153 the cellular localization and trafficking of EPCR in endothelial cells and a heterologous expression

154 rnalization and intracellular trafficking of EPCR-FVIIa.

155 apeutic efficacy of aPC, whereas transfer of EPCR-deficient CD11chi dendritic cells or wild-type CD11

156 DSS treatment of EPCR(-/-) mice resulted in increased bleeding, bodyweigh

157 Comprehensive understanding of EPCR may lead to development of novel therapeutic modali

158 y in severe sepsis is predominantly based on EPCR- and PAR1-dependent cell signaling, and APC variant

159 strictly required for PL membrane binding or EPCR recognition.

160 ing EPCR (EPCR-/-FVIII-/-) or overexpressing EPCR (EPCR++ FVIII-/-).

161 otic challenge with factor Xa/phospholipids, EPCR(R84A/R84A) mice generate more thrombin, less APC, a

162 of endothelial protein C receptor-positive (EPCR(+)) LT-HSCs in the bone marrow and their recruitmen

163 should be mimicked in immunogens to prevent EPCR binding.

164 we found that the protein C receptor (ProcR; EPCR) was required for the normal in vivo and in vitro i

165 activated protein C binding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocytosis may faci

166 We next observed rapid, EPCR and PI 3-kinase-dependent, APC-mediated phosphoryla

167 e binding to endothelial protein C receptor (EPCR) and cleavage of protease activated receptor-1 (PAR

168 require the endothelial protein C receptor (EPCR) and protease activated receptor 1 (PAR1).

169 eptors, endothelial cell protein C receptor (EPCR) and protease-activated receptor 1 (PAR1).

170 ding to endothelial cell protein C receptor (EPCR) and subsequent protease activated receptor (PAR)-1

171 lin (TM) and endothelial protein C receptor (EPCR) and that low constitutive expression of these regu

172 egulation of endothelial protein C receptor (EPCR) and thrombomodulin protein expressions, inhibited

173 The endothelial protein C receptor (EPCR) appears to play an important role in Plasmodium fa

174 The endothelial cell protein C receptor (EPCR) augments protein C activation by the thrombin-thro

175 against the endothelial protein C receptor (EPCR) binding CIDRalpha1 domains, and this difference wa

176 dies to endothelial cell protein C receptor (EPCR) blocked effectively (125)I-FVIIa binding to HUVEC.

177 occupancy of endothelial protein C receptor (EPCR) by the Gla-domain of protein C/APC is responsible

178 The endothelial protein C receptor (EPCR) confers anti-inflammatory properties when bound by

179 the role of endothelial protein C receptor (EPCR) in hemophilic arthropathy.

180 sion of endothelial cell protein C receptor (EPCR) in MPM cells suppresses tumorigenicity.

181 ding to endothelial cell protein C receptor (EPCR) induces anti-inflammatory signaling and protects v

182 Endothelial cell protein C receptor (EPCR) is a multifunctional and multiligand receptor, whi

183 f PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria.

184 e binding to endothelial protein C receptor (EPCR) is associated with severe disease has suggested ne

185 The endothelial protein C receptor (EPCR) is crucial for signaling by activated protein C th

186 The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood v

187 ow that endothelial cell protein C receptor (EPCR) is specifically expressed by mouse CD8+ dendritic

188 otein C with endothelial protein C receptor (EPCR) leads to dissociation of the receptor from caveoli

189 The endothelial protein C receptor (EPCR) limits thrombus formation by enhancing activation

190 Loss of endothelial protein C receptor (EPCR) occurs at the sites of Plasmodium falciparum-infec

191 loss of the endothelial protein C receptor (EPCR) on brain vessels, caused by cytoadherent infected

192 APC) to endothelial cell protein C receptor (EPCR) on endothelial cells.

193 olecule endothelial cell protein C receptor (EPCR) on MCs.

194 t for either endothelial protein C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling

195 The endothelial protein C receptor (EPCR) plays an important role in cardiovascular disease

196 e shown that endothelial protein C receptor (EPCR) polymorphisms and soluble EPCR levels are associat

197 vel APC-endothelial cell protein C receptor (EPCR) signaling pathway in endothelial cells.

198 cts with the endothelial protein C receptor (EPCR) through its gamma-carboxyglutamic acid (Gla) domai

199 ding of endothelial cell protein C receptor (EPCR) to its ligands is well characterized at the bioche

200 Endothelial cell protein C receptor (EPCR) was first identified and isolated as a cellular re

201 to the endothelial cell protein C receptor (EPCR), a cellular receptor for protein C and activated p

202 lates impair endothelial protein C receptor (EPCR), a protein involved in coagulation and endothelial

203 nteract with endothelial protein C receptor (EPCR), allowing infected erythrocytes to synergistically

204 ulin (THBD), endothelial protein C receptor (EPCR), and tissue factor pathway inhibitor (TFPI).

205 for soluble endothelial protein C receptor (EPCR), as demonstrated by surface plasmon resonance stud

206 domains bind endothelial protein C receptor (EPCR), CIDRalpha2-6 domains bind CD36, whereas the recep

207 lin (TM) and endothelial protein C receptor (EPCR), endothelial membrane proteins that partner in act

208 g the murine endothelial protein C receptor (EPCR), is expressed at high levels within the bone marro

209 suggest the endothelial protein C receptor (EPCR), known for its pivotal role in mediating cytoprote

210 require the endothelial protein C receptor (EPCR), protease-activated receptor (PAR) 1, and PAR3.

211 il receptors endothelial protein C receptor (EPCR), protease-activated receptor 3 (PAR3), and macroph

212 e quantified endothelial protein C receptor (EPCR), thrombomodulin (TM), and von Willebrand factor (V

213 rectly bound endothelial protein C receptor (EPCR), which allowed gammadelta T cells to recognize bot

214 pts encoding endothelial protein C receptor (EPCR)-binding domains, in combination with high parasite

215 through the endothelial protein C receptor (EPCR)-dependent cleavage of protease-activated receptor

216 through its endothelial protein C receptor (EPCR)-dependent cleavage of protease-activated receptor

217 nding to the endothelial protein C receptor (EPCR).

218 to the endothelial cell protein C receptor (EPCR).

219 , but not on endothelial protein C receptor (EPCR).

220 and the endothelial cell protein C receptor (EPCR).

221 lin (TM) and endothelial protein C receptor (EPCR).

222 ICAM-1), and endothelial protein C receptor (EPCR); however, cytoadhesion patterns typical for pediat

223 factor, endothelial cell protein C receptor (EPCR, PROCR), and protease activated receptor-1 (PAR1, F

224 ells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem

225 1 (PAR1) and endothelial protein C receptor (EPCR; also known as Procr).

226 ein C (PC) with the endothelial PC receptor (EPCR) enhances activated PC (APC) generation.

227 naling and the endothelial cell PC receptor (EPCR) prevented vascular leakage, and pharmacologic or g

228 or-alpha converting enzyme activity, reduced EPCR shedding, and restored plasma protein C level.

229 with activated protein C (aPC) that retains EPCR(+) LT-HSCs by limiting NO generation, reducing Cdc4

230 scFv/TM and scFv/EPCR bound to mouse endothelial PECAM-1 with high affini

231 odulin and EPCR) and APC cellular signaling (EPCR and PAR-1) pathways are colocalized in the membrane

232 C receptor (EPCR) polymorphisms and soluble EPCR levels are associated with thrombotic diseases.

233 a, which also possesses Leu-8, bound soluble EPCR with similar affinity to wild-type protein C, colle

234 pite consistent findings of elevated soluble EPCR (sEPCR) in other infectious diseases, field studies

235 he major phospholipid bound to human soluble EPCR (sEPCR).

236 ationships between endogenous plasma soluble EPCR (sEPCR) levels and clinical presentation or mortali

237 Here we show that soluble EPCR regulates the interaction of FX with human or mouse

238 There is a rationale for studying EPCR in hemophilia.

239 Consistent with the data that EPCR deficiency protects against developing hemophilic a

240 These results demonstrate that EPCR interacts with the ternary TF coagulation initiatio

241 In this study, we demonstrate that EPCR is associated with caveolin-1 in lipid rafts of end

242 We demonstrate that EPCR occupancy recruits G-protein coupled receptor kinas

243 In vitro studies demonstrated that EPCR expression renders MPM cells highly susceptible to

244 mmary, our data provide direct evidence that EPCR plays a crucial role in regulating the inflammation

245 resent data provide convincing evidence that EPCR serves as a cellular binding site for FVII/FVIIa.

246 The present data indicate that EPCR could be an attractive new target to prevent joint

247 Altogether, our results indicate that EPCR is a reliable and cell culture-compatible marker of

248 It is well recognized that EPCR promotes the activation of protein C (PC) to activa

249 Here, we report that EPCR is expressed in the colon epithelial cells, CD11c(+

250 However, they reported that EPCR blockade by itself did not reduce the severity of b

251 Immunohistochemical analyses revealed that EPCR expression in tumor cells reduced tumor cell prolif

252 thrombin infusion experiments revealed that EPCR heterozygosity (Procr+/-) impaired protein C activa

253 ansfected with PAR1 constructs revealed that EPCR occupancy initiates beta-arrestin-2 biased PAR1 sig

254 In summary, our data show that EPCR expression in MPM cells promotes tumor cell apoptos

255 In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-ne

256 main and dose titrations with FX showed that EPCR interacted primarily with FX to attenuate FX activa

257 lex to enable PAR signaling and suggest that EPCR may play a role in regulating the biology of TF-exp

258 after a severe malaria episode suggest that EPCR-binding PfEMP1 may have a role in the pathogenesis

259 in can also recruit thrombin to activate the EPCR-bound protein C, thereby eliciting PAR-1 signaling

260 iation complex of blood coagulation, and the EPCR-dependent activation of protease-activated receptor

261 Deletion of the EPCR gene (Procr) in mice leads to embryonic lethality b

262 ons of FVIIa were found to impair partly the EPCR-dependent protein C activation and APC-mediated cel

263 f 885 CIDRalpha1 sequences, showing that the EPCR-binding surfaces of CIDRalpha1 domains are conserve

264 C receptor (EPCR) or PAR1 revealed that the EPCR-dependent signaling activity of APC is primarily re

265 Using peptides corresponding to the EPCR-binding region, antibodies can be purified from ind

266 en inhibits the host immune response via the EPCR.

267 When the EPCR was blocked, F. tularensis lost the ability to supp

268 Antibodies to EPCR-binding domains increased from presentation to foll

269 d the binding affinities of protein C/APC to EPCR.

270 activated coagulation FVIIa can also bind to EPCR.

271 Pavani et al showed that binding to EPCR enhances the hemostatic effect of FVIIa in a mouse

272 FVIIa binding to EPCR failed to accelerate FVIIa activation of factor X o

273 FVIIa binding to EPCR is confirmed by demonstrating a marked increase in

274 FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand

275 t study, we show that FVIIa, upon binding to EPCR on endothelial cells, activates endogenous protease

276 Ia (FVIIa) or activated protein C binding to EPCR promoted the internalization of EPCR.

277 that FVIIa or activated protein C binding to EPCR promotes EPCR endocytosis, and EPCR-mediated endocy

278 The effects of APC binding to EPCR rapidly triggered Akt and extracellular signal-regu

279 FVIIa binding to EPCR was shown to facilitate FVIIa endocytosis.

280 in protein C/APC that favor their binding to EPCR.

281 nsequences and relevance of FVIIa binding to EPCR.

282 as competitive inhibitors for APC binding to EPCR.

283 nt data provide evidence that FVIIa bound to EPCR on endothelial cells activates PAR1-mediated cell s

284 in C, and activated protein C (APC) bound to EPCR with similar affinity.

285 ces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-alpha-co

286 Higher IgG levels to EPCR-binding CIDRalpha1 variants positively correlated w

287 -positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage repopul

288 FVIIa-induced, barrier-protective effect was EPCR dependent and did not involve PAR2.

289 Thus, when EPCR is bound by protein C, the PAR-1 cleavage-dependent

290 structures beneath the plasma membrane where EPCR and FVIIa accumulated.

291 s attenuated their growth potential, whereas EPCR silencing in nonaggressive MPM cells engineered to

292 resses MPM tumor growth and evaluate whether EPCR gene therapy could suppress the progression of MPM

293 Here, we study whether EPCR facilitates rhFVIIa hemostasis in hemophilia using

294 aimed to investigate the mechanism by which EPCR suppresses MPM tumor growth and evaluate whether EP

295 stem cell activity is always associated with EPCR-expressing cells.

296 -induced expression of TF and crosstalk with EPCR, PAR2, and TLR4 therefore appear necessary for the

297 es in mice showed that blockade of EPCR with EPCR-blocking antibodies impaired the early phase of FVI

298 or mechanism by which FVIIa interaction with EPCR contributes to the hemostatic effect of FVIIa in he

299 otential influence of FVIIa interaction with EPCR in the pathogenesis of hemophilic arthropathy and i

300 cells that had been stably transfected with EPCR compared with the wild-type.